ERBB2 Regulates MED24 during Cancer Progression in Mice with Pten and Smad4 Deletion in the Pulmonary Epithelium

ERBB2 is an oncogenic driver with frequent gene mutations and amplification in human lung tumors and is an attractive target for lung cancer therapy. However, target therapies can be improved by understanding the in vivo mechanisms regulated by ERBB2 during lung tumor development. Here, we generated genetic mouse models to show that <i>Erbb2</i> loss inhibited lung tumor development induced by deletion of <i>Pten</i> and <i>Smad4</i>. Transcriptome analysis showed that <i>Erbb2</i> loss suppressed the significant changes of most of the induced genes by ablation of <i>Pten</i> and <i>Smad4</i>. Overlapping with ERBB2-associated human lung cancer genes further identified those ERBB2 downstream players potentially conserved in human and mouse lung tumors. Furthermore, MED24 was identified as a crucial oncogenic target of ERBB2 in lung tumor development. Taken together, ERBB2 is required for the dysregulation of cancer-related genes, such as <i>MED24</i>, during lung tumor development.